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BRCA1 and BRCA2 mutations have been proven to place patients at higher risk for both breast cancer and ovarian cancer. Screening of high-risk women began in the mid 1990s without data to support what should be done in response to a positive finding. Since then, retrospective data has shown a 90% risk reduction in breast cancer with prophylactic bilateral mastectomies and a decrease in ovarian cancer and breast cancer with prophylactic salpingo-oopherectomy in patients with BRCA1 and BRCA2 mutations. This reports the results of the first study prospectively evaluating risk reduction in breast cancer and ovarian cancer with prophylactic risk reduction salpingo-oopherectomy (RRSO).

Materials and Methods

265/272 patients diagnosed with BRCA1 or BRCA2 mutations elected to participate in this prospective follow up study

88 patients were excluded from analysis due to prior salpingo-oopherectomy or age <35, leaving a study population of 173.

All were counseled regarding risks, the importance of frequent follow-up with physicians, self exams, as well as a discussion regarding prophylactic bilateral mastectomies and RRSO.

Women made their own decision regarding treatment (i.e.-RRSO or ovarian surveillance (OS))

Groups (RRSO vs. OS) were well-balanced with regards to type of BRCA mutation, prior breast cancer, prior chemotherapy, etc. However, in the RRSO group, 30% had prior prophylactic mastectomies compared to 16% in the OS group.

Results

101/173 elected to undergo RRSO

3 patients in the RRSO had early stage ovarian cancers in their pathologic specimen. These patients were excluded from primary analysis.

Projected % free from ovarian cancer was 98% for the RRSO group vs. 83% for the OS group

Projected % free from all cancers was 94% for the RRSO group vs. 69% for the OS group

Hazard ratio of RRSO was .21 (.37 if 3 cases of early ovarian cancers found at RRSO were included)

There were minor complications with surgery in approximately 5% of the patients

Author's Conclusions

RRSO reduces risk of breast or ovarian cancer by 75%

Patients should be counseled of risk of early stage ovarian cancer at diagnosis

Patients should be made aware of the small, but definite risk of complications in this preventive surgery.

Clinical/Scientific Implications

BRCA1 and BRCA2 mutations are perhaps the single most predictive risk factor for the development of breast and ovarian cancer. Although the efficacy of prophylactic mastectomies has been proven, this is the first study investigating the use of prophylactic oopherectomy in a prospective evaluation. As per the results of this study, RRSO appears to reduce the risk of developing breast and ovarian cancer in patients with BRCA1 and BRCA2 mutations. Although it should be noted that almost twice the number of patients had prior mastectomies in the RRSO group, the reduction in breast cancer is still likely to be significant. However, if a woman wishes to undergo prophylactic mastectomies rather than oopherectomies to reduce her breast cancer risk, that should be her perogative. Also, these recommendations should be tailored to the individual patient. Does the reduction of cancer risk justify RRSO? Is the 5% surgical morbidity acceptable? Are the data mature enough to be accepted? These questions should be considered when an individual patient is considering any preventive intervention. However, with this prospective data, patients can be better counseled with the assurance that risk reduction in breast and ovarian cancer with RRSO is supported.
Of note, this will be published as a full manuscript in the upcoming NEJM 346, 2002; 1609.

Apr 7, 2010 - Women who carry a BRCA1 or BRCA2 genetic mutation and develop breast cancer are at a substantially increased risk for contralateral breast cancer later on, according to research published online April 5 in the Journal of Clinical Oncology.